Summary of work: Alzheimer's disease (AD) is characterized by decreased brain energy metabolism, as has been shown by in vivo positron emission tomography (PET) studies done in our laboratory. We have shown that neurofibrillary tangles (NFTs) in postmortem brain samples from patients with AD are associated with decreased neuronal levels of a molecular marker of neuronal energy metabolism, cytochrome oxidase subunit III mRNA (COX III mRNA). However, NFTs may not be the cause of decreased energy metabolism in AD, because even tangle-free neurons in AD brains showed decreased levels of the marker compared with control tangle-free neurons. We have now examined energy metabolism in neurons close to neuritic plaques (NP), another pathologic hallmark of AD. Neurons close to NPs showed no decrease in levels of two energy metabolic markers (COX III mRNA and COX enzyme activity) compared with more distant neurons. In addition, total levels of COX III mRNA in brain samples showed no correlation with NP density. Therefore, NPs may not contribute to reduced neuronal energy metabolism in AD.